About 70% of activating EGFRm can be detected using CtDNA in patients with activating EGFRm in their Tumor DNA. The treatment efficacy of afatinib was assessed in patients with lung cancer harboring EGFRm which were detected from CtDNA. Primary objective was to prove overall response rate (ORR) in response evaluable population, and the secondary endpoints were progression free survival, overall survival and safety. Ten mL of venous blood was withdrawn and plasma preparation was finished as soon as possible, no more than 4 hours after draw. Plasma samples were stored at -20℃ until delivered to Panagene. EGFRm analyses for CtDNA were performed by PANA Mutyper® EGFR kit (Panagene, Korea). EGFRm testing for tumor DNA were performed by in-house testing in each hospital with PNA clamp EGFR mutation kit or PANA Mutyper® EGFR kit. A total of 340 (331 without missing values) patients were screened for this trial from 2015 July to 2018 March. Tumor genotyping showed 24.5% (81/331), while CtDNA showed 20.5% (68/331) of positivity to detect activating EGFRm (exon 19 deletions, exon 21 and exon 18 point mutations). Among 81 subjects with tumor DNA EGFRm positive subjects, 48 showed EGFRm in their CtDNA (59% sensitivity). Types of EGFRm were completely matched between tumor DNA and CtDNA in 48 subjects. Among 21 subjects enrolled in this trial, 11 subjects had EGFRm only in CtDNA (tumor DNA EGFR wild or unknown, Group 1), and 10 subjects had same EGFRm in their CtDNA and tumor DNA (Group 2). Afatinib (40mg) was initiated in 21 (female:17, adenocarcinoma:20, NSCLC-NOS:1) subjects with mean age of 68.5 years (standard deviation 8.7). Dose modifications were made in 13 subjects (62%). Partial remission was observed in 13 subjects, stable disease in 6 subjects, and response was not evaluated in 2 subjects (ORR : 68.4%). There was no significant difference (p=0.35) in ORR between Group 1 (80%) and Group 2 (55.6%). As of July 25 2018, treatment is ongoing in 15 subjects, progression was confirmed in 3 subjects and 1 withdrew consent, 2 discontinued treatment due to serious adverse events (SAEs). A total of 5 SAEs including 2 subjects with possible drug induced lung disease were reported. In conclusion, afatinib showed favorable efficacy in subjects with NSCLC harboring EGFRm in their CtDNA. Acknowledgement: This study was funded by Boehringer Ingelheim and Panagene. ClinicalTrials.gov Identifier: NCT02629523.